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http://hdl.handle.net/1843/77711| Tipo: | Artigo de Periódico |
| Título: | Calix[6]arene diminishes receptor tyrosine kinase lifespan in pancreatic cancer cells and inhibits their migration and invasion efficiency |
| Autor(es): | Karin Juliane Pelizzaro Rocha-Brito Emanuella Maria Barreto Fonseca Breno Germano de Freitas Oliveira Ângelo de Fátima Carmen Veríssima Ferreira-Halder |
| Resumen: | Pancreatic cancer is a challenging malignancy, mainly due to aggressive regional involvement, early systemic dissemination, high recurrence rate, and subsequent low patient survival. Scientific advances have contributed in particular by identification of molecular targets as well as the definition of the mechanism of action of the drug candidate in the cellular microenvironment. Previously, we have reported the identification of the molecular mechanisms by which calix[6]arene (CLX6) reduces the viability and proliferation of pancreatic cancer cells. Now, we show the biochemical mechanisms by which CLX6 decreases the aggressiveness of Panc-1 cells, focusing specifically on receptor tyrosine kinases (RTK). The results show that clathrin-mediated endocytosis is involved in CLX6-induced AXL receptor tyrosine kinase degradation in Panc-1 cells. This response may be related to the interaction of CLX6 with the tyrosine kinase receptor binding site (such as AXL). As a result, RTK is internalized and degraded by endocytosis, a condition that negatively impacts events dependent on its signaling. Additionally, CLX6 inhibits migration and invasion of Panc-1 cells by downregulating FAK (downstream mediator of AXL) activity and reducing expression levels of MMP2 and MMP9, directly related to the metastatic profile of these cells. It is noteworthy that according to the mechanism proposed here, CLX6 appears as a candidate to be used in therapeutic protocols of patients that display high expression of AXL and consequently, poor diagnosis. |
| Asunto: | Calixarenos Cancer -Tratamento Metástase Células cancerosas - Proliferação |
| Idioma: | eng |
| País: | Brasil |
| Editor: | Universidade Federal de Minas Gerais |
| Sigla da Institución: | UFMG |
| Departamento: | ICX - DEPARTAMENTO DE QUÍMICA |
| Tipo de acceso: | Acesso Restrito |
| Identificador DOI: | https://doi.org/10.1016/j.bioorg.2020.103881 |
| URI: | http://hdl.handle.net/1843/77711 |
| Fecha del documento: | 2020 |
| metadata.dc.url.externa: | https://www.sciencedirect.com/science/article/pii/S0045206820303138 |
| metadata.dc.relation.ispartof: | Bioorganic Chemistry |
| Aparece en las colecciones: | Artigo de Periódico |
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